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Diclofenac affects kidney histology in the three-spined stickleback (Gasterosteus aculeatus) at low mu g/L concentrations

Journal article
Authors J. Naslund
J. Fick
Noomi Asker
E. Ekman
D. G. Joakim Larsson
L. Norrgren
Published in Aquatic Toxicology
Volume 189
Pages 87-96
ISSN 0166-445X
Publication year 2017
Published at Department of Biological and Environmental Sciences
Institute of Biomedicine, Department of Infectious Medicine
Pages 87-96
Language en
Links dx.doi.org/10.1016/j.aquatox.2017.0...
Keywords Diclofenac, Fish, Histology, Kidney, Quantitative PCR, Bioconcentration, ENVIRONMENTALLY RELEVANT CONCENTRATIONS, TROUT ONCORHYNCHUS-MYKISS, RAINBOW-TROUT, PHARMACEUTICAL DICLOFENAC, GILL INTEGRITY, FISH, RESPONSES, DIBENZANTHRACENE, BIOCONCENTRATION, HISTOPATHOLOGY, Marine & Freshwater Biology, Toxicology, X GA, 1991, JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTHINTERNATIONAL JOINT
Subject categories Marine ecology, Toxicology

Abstract

Diclofenac, a commonly used non-steroidal anti-inflammatory drug, is considered for regulation under the European water framework directive. This is because effects on fish have been reported at concentrations around those regularly found in treated sewage effluents (similar to 1 mu g/L). However, a recent publication reports no effects on fish at 320 mu g/L. In this study, three-spined sticklebacks (Gasterosteus aculeatus) were exposed to 0, 4.6, 22, 82 and 271 mu g/L diclofenac in flow-through systems for 28 days using triplicate aquaria per concentration. At the highest concentration, significant mortalities were observed already after 21 days (no mortalities found up to 22 mu g/L). Histological analysis revealed a significant increase in the proportion of renal hematopoietic tissue (renal hematopoietic hyperplasia) after 28 days at the lowest concentration and at all higher concentrations, following a clear dose-response pattern. Skin ulcerations of the jaw were noted by macroscopic observations, primarily at the two highest concentrations. No histological changes were observed in the liver. There was an increase in the relative hepatic mRNA levels of c7 (complement component 7), a gene involved in the innate immune system, at 22 mu g/L and at all higher concentrations, again following a clear dose-response. The bio-concentration factor was stable across concentrations, but lower than reported for rainbow trout, suggesting lower internal exposure to the drug in the stickleback. In conclusion, this study demonstrates that diclofenac causes histological changes in the three-spined stickleback at low mu g/L concentrations, which cause concern for fish populations exposed to treated sewage effluents.

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